Trial Outcomes & Findings for Lubiprostone for the Treatment of Chronic Idiopathic Constipation (NCT NCT02651155)

NCT ID: NCT02651155

Last Updated: 2018-08-13

Results Overview

A SBM is defined as any bowel movement (BM) that does not occur within 24 hours after rescue medication use (laxative, suppository, or enema). SBM frequency data was collected in a diary. Participants were given a diary to complete at home where they recorded the date and time of each BM.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

204 participants

Primary outcome timeframe

Week 1

Results posted on

2018-08-13

Participant Flow

Participants took part in the study at 20 investigative sites in Russia from 17 February 2016 to 26 January 2017.

Participants with a diagnosis of chronic idiopathic constipation as determined by the Rome III Diagnostic Criteria for Functional Constipation were enrolled in 1:1 ratio to receive lubiprostone or placebo.

Participant milestones

Participant milestones
Measure
Placebo
Lubiprostone placebo-matching capsules, orally, twice daily, for up to 4 weeks.
Lubiprostone 24 μg
Lubiprostone 24 μg, capsules, orally, twice daily, for up to 4 weeks.
Overall Study
STARTED
99
105
Overall Study
COMPLETED
93
103
Overall Study
NOT COMPLETED
6
2

Reasons for withdrawal

Reasons for withdrawal
Measure
Placebo
Lubiprostone placebo-matching capsules, orally, twice daily, for up to 4 weeks.
Lubiprostone 24 μg
Lubiprostone 24 μg, capsules, orally, twice daily, for up to 4 weeks.
Overall Study
Pretreatment Event/Adverse Event
1
2
Overall Study
Voluntary Withdrawal
5
0

Baseline Characteristics

Lubiprostone for the Treatment of Chronic Idiopathic Constipation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Placebo
n=99 Participants
Lubiprostone placebo-matching capsules, orally, twice daily, for up to 4 weeks.
Lubiprostone 24 μg
n=105 Participants
Lubiprostone 24 μg, capsules, orally, twice daily, for up to 4 weeks.
Total
n=204 Participants
Total of all reporting groups
Age, Continuous
49.0 years
n=5 Participants
51.1 years
n=7 Participants
50.1 years
n=5 Participants
Sex: Female, Male
Female
81 Participants
n=5 Participants
90 Participants
n=7 Participants
171 Participants
n=5 Participants
Sex: Female, Male
Male
18 Participants
n=5 Participants
15 Participants
n=7 Participants
33 Participants
n=5 Participants
Race/Ethnicity, Customized
Asian
0 participants
n=5 Participants
1 participants
n=7 Participants
1 participants
n=5 Participants
Race/Ethnicity, Customized
White
99 participants
n=5 Participants
102 participants
n=7 Participants
201 participants
n=5 Participants
Race/Ethnicity, Customized
Multiracial
0 participants
n=5 Participants
2 participants
n=7 Participants
2 participants
n=5 Participants
Region of Enrollment
Russia
99 participants
n=5 Participants
105 participants
n=7 Participants
204 participants
n=5 Participants
Height
166.2 cm
STANDARD_DEVIATION 7.16 • n=5 Participants
165.1 cm
STANDARD_DEVIATION 7.77 • n=7 Participants
165.6 cm
STANDARD_DEVIATION 7.49 • n=5 Participants
Weight
70.08 kg
STANDARD_DEVIATION 14.206 • n=5 Participants
68.75 kg
STANDARD_DEVIATION 11.240 • n=7 Participants
69.39 kg
STANDARD_DEVIATION 12.751 • n=5 Participants
Body Mass Index
25.265 kg/m^2
STANDARD_DEVIATION 4.2558 • n=5 Participants
25.254 kg/m^2
STANDARD_DEVIATION 4.0513 • n=7 Participants
25.259 kg/m^2
STANDARD_DEVIATION 4.1415 • n=5 Participants
Smoking Classification
Participant has never smoked
87 participants
n=5 Participants
88 participants
n=7 Participants
175 participants
n=5 Participants
Smoking Classification
Participant is a current smoker
9 participants
n=5 Participants
11 participants
n=7 Participants
20 participants
n=5 Participants
Smoking Classification
Participant is an ex-smoker
3 participants
n=5 Participants
6 participants
n=7 Participants
9 participants
n=5 Participants

PRIMARY outcome

Timeframe: Week 1

Population: FAS included all participants who were randomized to receive study treatment whether or not they received treatment. Missing values were imputed by last observation carried forward (LOCF) method.

A SBM is defined as any bowel movement (BM) that does not occur within 24 hours after rescue medication use (laxative, suppository, or enema). SBM frequency data was collected in a diary. Participants were given a diary to complete at home where they recorded the date and time of each BM.

Outcome measures

Outcome measures
Measure
Placebo
n=99 Participants
Lubiprostone placebo-matching capsules, orally, twice daily, for up to 4 weeks.
Lubiprostone 24 μg
n=105 Participants
Lubiprostone 24 μg, capsules, orally, twice daily, for up to 4 weeks.
Spontaneous Bowel Movement (SBM) Frequency at Week 1
3.6 SBMs/week
Standard Deviation 2.51
5.0 SBMs/week
Standard Deviation 2.94

SECONDARY outcome

Timeframe: Weeks 2, 3 and 4

Population: FAS included all participants who were randomized to receive study treatment whether or not they received treatment. Missing values were imputed by LOCF method.

A SBM is defined as any BM that does not occur within 24 hours after rescue medication use. SBM frequency data was collected in a diary. Participants were given a diary to complete at home where they recorded the date and time of each BM.

Outcome measures

Outcome measures
Measure
Placebo
n=99 Participants
Lubiprostone placebo-matching capsules, orally, twice daily, for up to 4 weeks.
Lubiprostone 24 μg
n=105 Participants
Lubiprostone 24 μg, capsules, orally, twice daily, for up to 4 weeks.
SBM Frequency at Weeks 2, 3 and 4
Week 2
3.9 SBMs/week
Standard Deviation 2.52
5.0 SBMs/week
Standard Deviation 2.82
SBM Frequency at Weeks 2, 3 and 4
Week 3
3.8 SBMs/week
Standard Deviation 2.87
5.1 SBMs/week
Standard Deviation 2.72
SBM Frequency at Weeks 2, 3 and 4
Week 4
3.7 SBMs/week
Standard Deviation 2.72
5.2 SBMs/week
Standard Deviation 2.61

SECONDARY outcome

Timeframe: Up to 24 hours after the first dose of study medication

Population: FAS included all participants who were randomized to receive study treatment whether or not they received treatment.

A SBM is defined as any BM that does not occur within 24 hours after rescue medication use. Percentage of participants who had a SBM within 24 hours after the first dose was assessed and derived from the data on SBMs collected in the participant diary.

Outcome measures

Outcome measures
Measure
Placebo
n=99 Participants
Lubiprostone placebo-matching capsules, orally, twice daily, for up to 4 weeks.
Lubiprostone 24 μg
n=105 Participants
Lubiprostone 24 μg, capsules, orally, twice daily, for up to 4 weeks.
Percentage of Participants Who Had a SBM Within 24 Hours After the First Dose of Study Medication
35.4 percentage of participants
46.7 percentage of participants

SECONDARY outcome

Timeframe: Weeks 1, 2, 3 and 4

Population: FAS included all participants who were randomized to receive study treatment whether or not they received treatment. Missing values were imputed by LOCF method.

For each participant, the mean degree of straining was averaged for all SBMs in a given week. The degree of straining for each SBM was collected in the participant diary. The degree of straining is scored on a 5-point scale where: 0=No straining, 1=Mild straining, 2=Moderate straining, 3=Strong straining or 4=Very strong straining with higher scores indicating more severe straining.

Outcome measures

Outcome measures
Measure
Placebo
n=99 Participants
Lubiprostone placebo-matching capsules, orally, twice daily, for up to 4 weeks.
Lubiprostone 24 μg
n=105 Participants
Lubiprostone 24 μg, capsules, orally, twice daily, for up to 4 weeks.
Mean Degree of Straining Score
Week 1
2.3 scores on a scale
Standard Deviation 1.09
1.7 scores on a scale
Standard Deviation 1.01
Mean Degree of Straining Score
Week 2
2.0 scores on a scale
Standard Deviation 1.11
1.6 scores on a scale
Standard Deviation 1.04
Mean Degree of Straining Score
Week 3
1.9 scores on a scale
Standard Deviation 1.19
1.4 scores on a scale
Standard Deviation 0.99
Mean Degree of Straining Score
Week 4
2.0 scores on a scale
Standard Deviation 1.19
1.3 scores on a scale
Standard Deviation 1.00

SECONDARY outcome

Timeframe: Weeks 1, 2, 3 and 4

Population: FAS included all participants who were randomized to receive study treatment whether or not they received treatment. Missing values were imputed by LOCF method.

For each participant, the mean stool consistency score was averaged for all SBMs in a given week. The mean degree of stool consistency for each SBM was collected in the participant diary based on the Bristol Stool Chart. The Bristol Stool Chart is a visual medical aid designed to classify the form of human feces into seven categories where: 1=Hard and round (difficult-to-pass), 2=Sausage-shaped but hard stool, 3=Sausage-shaped stool with cracks on the surface, 4=Sausage-shaped, soft stool with smooth surface, or coiled stool, 5=Soft, half-solid (and easy-to-pass) stool with clear crease, 6=Unshaped, loose stool with small, irregular-shaped pieces, or mushy stool or 7=Watery stool without solid pieces (entirely liquid).

Outcome measures

Outcome measures
Measure
Placebo
n=99 Participants
Lubiprostone placebo-matching capsules, orally, twice daily, for up to 4 weeks.
Lubiprostone 24 μg
n=105 Participants
Lubiprostone 24 μg, capsules, orally, twice daily, for up to 4 weeks.
Mean Degree Stool Consistency Score
Week 1
3.0 scores on a scale
Standard Deviation 1.10
3.6 scores on a scale
Standard Deviation 1.37
Mean Degree Stool Consistency Score
Week 2
3.3 scores on a scale
Standard Deviation 1.08
3.7 scores on a scale
Standard Deviation 1.33
Mean Degree Stool Consistency Score
Week 3
3.2 scores on a scale
Standard Deviation 1.11
3.8 scores on a scale
Standard Deviation 1.28
Mean Degree Stool Consistency Score
Week 4
3.0 scores on a scale
Standard Deviation 1.06
3.8 scores on a scale
Standard Deviation 1.30

SECONDARY outcome

Timeframe: Weeks 1, 2, 3 and 4

Population: FAS included all participants who were randomized to receive study treatment whether or not they received treatment. Missing values were imputed by LOCF method.

The abdominal symptoms (bloating and discomfort upon waking in the morning) were scored weekly on a 5-point scale, where: 0=None, 1=Mild, 2=Moderate, 3=Severe or 4=Very severe, with a higher score indicating more severe symptoms. Assessment of weekly abdominal symptoms were recorded by the participant in the diary.

Outcome measures

Outcome measures
Measure
Placebo
n=99 Participants
Lubiprostone placebo-matching capsules, orally, twice daily, for up to 4 weeks.
Lubiprostone 24 μg
n=105 Participants
Lubiprostone 24 μg, capsules, orally, twice daily, for up to 4 weeks.
Weekly Abdominal Symptoms Score
Abdominal Bloating, Week 1
1.6 scores on a sclae
Standard Deviation 1.00
1.5 scores on a sclae
Standard Deviation 0.86
Weekly Abdominal Symptoms Score
Abdominal Bloating, Week 2
1.5 scores on a sclae
Standard Deviation 1.04
1.3 scores on a sclae
Standard Deviation 0.94
Weekly Abdominal Symptoms Score
Abdominal Bloating, Week 3
1.6 scores on a sclae
Standard Deviation 1.02
1.2 scores on a sclae
Standard Deviation 1.01
Weekly Abdominal Symptoms Score
Abdominal Bloating, Week 4
1.4 scores on a sclae
Standard Deviation 1.03
1.1 scores on a sclae
Standard Deviation 0.93
Weekly Abdominal Symptoms Score
Abdominal Discomfort, Week 1
1.7 scores on a sclae
Standard Deviation 0.98
1.5 scores on a sclae
Standard Deviation 0.95
Weekly Abdominal Symptoms Score
Abdominal Discomfort, Week 2
1.6 scores on a sclae
Standard Deviation 1.07
1.3 scores on a sclae
Standard Deviation 0.98
Weekly Abdominal Symptoms Score
Abdominal Discomfort, Week 3
1.6 scores on a sclae
Standard Deviation 1.06
1.2 scores on a sclae
Standard Deviation 1.01
Weekly Abdominal Symptoms Score
Abdominal Discomfort, Week 4
1.5 scores on a sclae
Standard Deviation 1.02
1.2 scores on a sclae
Standard Deviation 0.97

Adverse Events

Placebo

Serious events: 1 serious events
Other events: 6 other events
Deaths: 0 deaths

Lubiprostone 24 μg

Serious events: 0 serious events
Other events: 16 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Placebo
n=99 participants at risk
Lubiprostone placebo-matching capsules, orally, twice daily, for up to 4 weeks.
Lubiprostone 24 μg
n=105 participants at risk
Lubiprostone 24 μg, capsules, orally, twice daily, for up to 4 weeks.
Nervous system disorders
Haemorrhagic stroke
1.0%
1/99 • Baseline and up to Week 6
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
0.00%
0/105 • Baseline and up to Week 6
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Other adverse events

Other adverse events
Measure
Placebo
n=99 participants at risk
Lubiprostone placebo-matching capsules, orally, twice daily, for up to 4 weeks.
Lubiprostone 24 μg
n=105 participants at risk
Lubiprostone 24 μg, capsules, orally, twice daily, for up to 4 weeks.
Gastrointestinal disorders
Nausea
3.0%
3/99 • Baseline and up to Week 6
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
10.5%
11/105 • Baseline and up to Week 6
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders
Diarrhoea
3.0%
3/99 • Baseline and up to Week 6
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
7.6%
8/105 • Baseline and up to Week 6
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Results disclosure agreements

  • Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
  • Publication restrictions are in place

Restriction type: OTHER